Age-related effects of acidosis in isolated cardiac muscle.
Acidosis is associated with myocardial ischemia and several reports indicate the greater vulnerability of the aged heart to ischemic dysfunction. We investigated the effects of hypercapnic acidosis on isolated heart (n = 14) and papillary muscle (n = 10) from adult and senescent rats. Acidosis (pH from 7.36 to 6.91) induced a decrease in left ventricular developed pressure together with an increase in left ventricular end-diastolic pressure, but was significantly more evident in senescent than in adult hearts (p < .01). The return to normal pH induced a further increase in the end-diastolic pressure parallel to the development of arrhythmias that were greater in senescent than in adult hearts. In isolated papillary muscle, acidosis confirmed its greater negative inotropic effect on senescent than adult muscles (p < .01), while intracellular sodium activity (aNai) increased to a similar extent in both adult and senescent papillary muscles (p = NS). 5-(N,N-dimethyl)-amiloride hydrochloride (DMA), a specific inhibitor of Na+/H+ exchanger, produced similar modification of tension and aNai in both adult and senescent muscles. When DMA was superfused in acidotic solution, the contractility was markedly compromised in senescent than in adult muscles (p < .01), but the aNai modifications were similar in adult and senescent muscles (p = NS). Our results show that acidosis induced a greater reduction of contractility in senescent than in adult hearts. The similarity of contractility during DMA administration between adult and senescent muscle and of modifications of aNai suggests that depression of contractility with acidosis may be related to pathophysiologic mechanisms other than the Na+/H+ exchanger.
Abete
P
P
Istituto di Medicina Interna, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli Federico II, Naples, Italy.
Ferrara
P
P
Bianco
S
S
Calabrese
C
C
Napoli
C
C
Cacciatore
F
F
Ferrara
N
N
Rengo
F
F
D000138:Acidosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D003971:Diastole; D004232:Diuretics / Q000494:pharmacology; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000150:complications; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D017725:Ventricular Pressure / Q000502:physiology
D004232:Diuretics; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D012964:Sodium